rs16908114

Positions:

• chr11-4992236-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021801.5(MMP26):​c.780A>G​(p.Ile260Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00332 in 1,610,454 control chromosomes in the GnomAD database, including 167 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.018 (83 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (84 hom.)
• Consequence: MMP26 NM_021801.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67

Genes affected

MMP26 (HGNC:14249): (matrix metallopeptidase 26) Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. The encoded preproprotein is proteolytically processed to generate the mature enzyme. This enzyme may degrade collagen type IV, fibronectin, fibrinogen, and beta-casein, and activate matrix metalloproteinase-9 by cleavage. The protein differs from most MMP family members in that it lacks a conserved C-terminal protein domain. The encoded protein may promote cell invasion in multiple human cancers. [provided by RefSeq, May 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0037540793).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP26	NM_021801.5	c.780A>G	p.Ile260Met	missense_variant	8/8	ENST00000380390.6
MMP26	NM_001384608.1	c.570A>G	p.Ile190Met	missense_variant	8/8
MMP26	XM_011520219.3	c.570A>G	p.Ile190Met	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP26	ENST00000380390.6	c.780A>G	p.Ile260Met	missense_variant	8/8	5	NM_021801.5	P1
MMP26	ENST00000300762.2	c.570A>G	p.Ile190Met	missense_variant	8/8	1
MMP26	ENST00000690848.1	c.780A>G	p.Ile260Met	missense_variant	7/7			P1

Frequencies

GnomAD3 genomes AF: 0.0183 AC: 2782 AN: 151692 Hom.: 80 Cov.: 32

Gnomad AFR AF: 0.0639

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00684

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0139

GnomAD3 exomes AF: 0.00480 AC: 1172 AN: 244120 Hom.: 45 AF XY: 0.00330 AC XY: 437 AN XY: 132376

Gnomad AFR exome AF: 0.0677

Gnomad AMR exome AF: 0.00265

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000667

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000165

Gnomad OTH exome AF: 0.00236

GnomAD4 exome AF: 0.00175 AC: 2550 AN: 1458644 Hom.: 84 Cov.: 32 AF XY: 0.00151 AC XY: 1096 AN XY: 725560

Gnomad4 AFR exome AF: 0.0627

Gnomad4 AMR exome AF: 0.00287

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000693

Gnomad4 OTH exome AF: 0.00389

GnomAD4 genome AF: 0.0184 AC: 2793 AN: 151810 Hom.: 83 Cov.: 32 AF XY: 0.0181 AC XY: 1339 AN XY: 74164

Gnomad4 AFR AF: 0.0640

Gnomad4 AMR AF: 0.00683

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.0138

Alfa AF: 0.00326 Hom.: 24

Bravo AF: 0.0211

ESP6500AA AF: 0.0652 AC: 287

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00588 AC: 714

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.054
DANN	Benign	0.059
DEOGEN2	Benign	0.0078	T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00021	N
MetaRNN	Benign	0.0038	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.060	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.89	N;N
REVEL	Benign	0.082
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	B;B
Vest4		0.036
MVP		0.092
MPC		0.070
ClinPred		0.0033	T
GERP RS		-2.3
Varity_R		0.036
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16908114; hg19: chr11-5013466;